Sex-Based Assessment of Patient Presentation, Lesion Characteristics and Treatment Modalities in Patients Undergoing Peripheral Vascular Intervention

Abstract

Background:

Limited evidence suggests that women and men might be treated differently for peripheral arterial disease (PAD). This analysis evaluated sex-based differences in disease presentation and its effect on treatment modality among patients who underwent endovascular treatment for PAD.

Methods and Results:

Using national registry data from the Vascular Quality Initiative between 2010–2013, we examined patient, limb, and artery characteristics by sex through descriptive statistics. We studied 26,750 procedures performed in 23,820 patients to treat 30,545 limbs and 44,804 arteries. Women presented at an older age (69 vs 67 years, p<0.001) and were less often current or former smokers (72% vs 85%, p<0.001). TASC classification was similar among men and women (TASC C or D: 37% in men vs 37% in women, p=0.81), as was mean occlusion length (4.5cm in men vs 4.6cm in women, p=0.04), even after accounting for lesion location. Women more frequently underwent treatment for rest pain (11% in men vs 16% in women, p<0.001) versus claudication (59% in men vs 53% in women, p<0.001) or tissue loss (28% in men vs 27% in women, p=0.75). Treatment modality did not differ by sex, but was associated with disease severity (p for trend<0.001) and lesion location (p for trend<0.001).

Conclusions:

Women undergo PVI for PAD at an older age with critical limb ischemia. Treatment modalities do not vary by sex, but are determined by disease severity and site. While there exist sex differences in presentation, these differences do not lead to differential treatment for women with PAD.

Elderly patients (age 65 and older) constitute the fastest growing segment of the United States population, and women outnumber men in this demographic group.^1–3 As the population ages, the prevalence of PAD will create substantial financial and resource burdens on the healthcare system.⁴ Moreover, according to the 2010 United States Census, the prevalence of PAD is higher in women than men.² Yet PAD remains under-recognized and under-treated among women.^{2, 5} Previous studies suggest that compared to men, women are treated at an older age, present with advanced multilevel disease,¹ have poorer overall health status, including more severe symptoms and lower quality of life, and are at increased risk for morbidity and mortality.⁶

Solitary investigations examined several aspects of sex bias in therapy, but these were not the primary objective of investigations and were likely underpowered to determine sex-based differences.^{6, 7} Furthermore, women remain an under-represented minority in most PAD studies, and many investigations have limited descriptions of clinical indications, treatment modalities, and disease distribution by sex.^{2, 4, 7} These factors were highlighted by the American Heart Association’s call to evaluate sex-based differences in the presentation of PAD with a goal to identify the potential variation in treatment approaches, benefits and harms among men compared to women.⁸

To better understand sex-based treatments for PAD, we sought to investigate differences in patient presentation, disease distribution, and treatment modalities among men and women undergoing peripheral endovascular intervention (PVI) for PAD. We utilized the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) dataset to analyze these characteristics among men and women.

Methods

Data Source

Established in 2011, the VQI prospectively collects data on over 120 patient and procedure-level variables for commonly performed major vascular procedures, such as PVI, at over 350 participating centers nationwide.⁹ For this project, we queried the VQI PVI dataset and abstracted all relevant patient and procedure variables. The data and analytic methods are available to other researchers pending approval by the Research Advisory Committee at VQI.

Establishing the Cohort

Patients who underwent PVI from January 1, 2010 to December 31, 2013 were eligible for inclusion in our analysis. There were 35,199 eligible PVI procedures performed in 28,173 patients. We excluded procedures with missing information on sex, indication, side treated, and artery treated (n=2,469; 7%). We also excluded interventions on a previously treated artery (n=2,405; 7%), aneurysmal disease pathology (n=339; 1%), and acute limb ischemia as indication for treatment (n=3,113; 9%). After applying these criteria, we had 26,873 procedures performed in 23,940 patients, 30,668 limbs, and 44,927 arteries (Figure 1). For analysis, we further excluded cases in which only the aorta was treated (n=123) since this is a different subgroup of pathology within our population of “peripheral” vascular disease. The final cohort for analysis included 26,750 procedures performed in 23,820 patients, 30,545 limbs, and 44,804 arteries.

Figure 1:

Creating the Cohort. This flowchart depicts the inclusion and exclusion criteria applied to each procedure in the registry to form the analytic cohort. This cohort was analyzed in three approaches, as outlined above: by patient, by limb, and by artery treated. For illustrative purposes, this diagram includes the number of eligible aorta only treatments (n=123), however these procedures were not included in any analyses.

Measures

The primary exposure was sex (men versus women). As shown in Figure 1, we analyzed our cohort in three different ways: by patient, by limb, and by artery treated. At the patient level, we studied sex-based differences in demographics and comorbidities. At the limb level, we examined the history of prior procedures, indication for treatment (claudication versus rest pain versus tissue loss), and unilateral versus bilateral treatment. Finally, at the artery level, we studied sex differences in type and number of arteries treated, lesion characteristics, and treatment modality utilized for each artery treated. Tibial arteries (anterior tibial, posterior tibial, peroneal, and tibio-peroneal trunk) were grouped together for analysis given their individual low frequency of treatment.

Statistical Analysis

Descriptive univariate statistics were conducted for all characteristics, stratified by sex. We also present absolute standardized differences (d) between men and women, which is a measure of the effect size (difference in means or proportions divided by the standard deviation). We used d > 0.1 as an threshold for imbalance, or significant difference, between the groups¹⁰. Statistical significance was determined using the Chi-Square Test of Independence and Student’s T-test for continuous variables. Since the focus of this paper is in the description of current practice, we did not use a formal method to account for multiple testing and present the uncorrected p-values. Although we refer to p<0.05 as a threshold for statistical significance, we focused on absolute difference of frequencies to identify significant and clinically meaningful findings. Linear trend analysis for categorical characteristics was conducted using simple logistic regression. All statistical analyses were performed using Stata 13.1 software (College Station, TX). Our study was designated as IRB exempt by the Center for the Protection of Human Subjects at the Geisel School of Medicine at Dartmouth.

Results

Cohort Characteristics

Women comprised 42% of our cohort. The mean age of patients was 68 years. Unilateral limb treatment was performed in 84% of patients and right and left limbs were treated with equal frequency. The aorta was primarily treated in conjunction with bilateral limb therapy (60% of all aortic treatments). The proportion of interventions at each arterial level were as follows, listed in descending order of frequency: superficial femoral artery (29%), common iliac artery (22%), popliteal artery (14%), external iliac artery (13%), anterior tibial artery (6%), tibio-peroneal trunk (4%), posterior tibial artery (4%), peroneal artery (4%), common femoral artery (4%), profunda femoris artery (1%), and aorta (1%).

Characteristics at Presentation

Most demographic characteristics at time of the index procedure were similar for men and women (Table 1). However, women presented at an older age than men (69 years versus 67 years, p<0.001, d=0.23) and were more likely to be African-American (15% vs 11%, p<0.001, d=0.14). Further, women were less likely to have a history of coronary disease (26% versus 32%, p<0.001, d=0.14), less likely to be ambulatory (77% versus 82% ambulatory, p<0.001, d=0.11) and were more commonly non-smokers (28% versus 15%, p<0.001, d=0.31). In terms of medications, women were less likely to be on a statin before the procedure (64% versus 70%, p<0.001, d=0.12)

Table 1.

Patient and limb characteristics of study population for patients.

Patient Characteristics	Men n=13,935	Women n=9,885	p-value†	Absolute Standardized Difference
Demographics
Race			<0.001
African-American	11 %	15 %		0.14
Caucasian	85 %	81 %		0.11
Other/unknown	4.1 %	3.7 %		0.02
Hispanic or Latino	4.4 %	4.2 %	0.334	0.01
Age mean years (SD)	67 (11)	69 (12)	<0.001	0.23
Living Location			<0.001
Home	97 %	96 %		0.05
Nursing home	3.3 %	4.4 %		0.06
Homeless	0.2 %	<0.1 %		0.04
Transfer from Hospital/Rehab	4.2 %	4.5 %	0.323	0.01
Comorbidities, Medication, and Ambulation
Smoking History % yes			<0.001
Never smoked	15 %	28 %		0.31
Prior smoker	45 %	37 %		0.17
Current smoker	40 %	36 %		0.09
Hypertension, % yes	87 %	88 %	0.151	0.02
Diabetes % yes	51 %	47 %	<0.001	0.08
Insulin-dependent Diabetes % yes	28 %	26 %	<0.001	0.03
CAD % yes	32 %	26 %	<0.001	0.14
CHF % yes	16 %	16 %	0.232	0.02
COPD % yes	22 %	25 %	<0.001	0.06
Dialysis % yes	6.9 %	6.5 %	0.001	0.02
ASA Classification			0.453
1-Normal/healthy	2.0 %	1.8 %		0.01
2-Mild systemic disease	28 %	27 %		0.02
3-Severe systemic disease	63 %	64 %		0.02
4-Disease is threat to life	7.7 %	7.5 %		0.01
5-Moribund	0.1 %	0.1 %		0.01
Ambulatory Status			<0.001
Ambulatory	82 %	77 %		0.11
Ambulatory with	13 %	17 %		0.10
assistance	4.5 %	5.5 %		0.04
Wheelchair	0.5 %	0.8 %		0.03
Bedridden
Statin % yes	70%	64%	<0.001	0.12
Beta Blocker % yes	58%	56%	0.002	0.04
Anticoagulant % yes	9.3%	8.4%	0.017	0.03
Aspirin or P2Y12 Antagonist % yes	80 %	78 %	<0.001	0.05
Limb Characteristics	Men n=17,740	Women n=12,805	p-value†	Absolute Standardized Difference
Symptom Severity
Indication			<0.001
Claudication	59 %	53 %		0.11
Rest Pain	11 %	16 %		0.14
Tissue Loss	28 %	27 %		0.01
Other*	2.0 %	3.0 %		0.06
Previous Intervention
Inflow
PTA/Stent/Atherectomy	10 %	11 %	0.789	<0.01
Ipsilateral limb	10 %	9.7 %	0.210	0.01
Contralateral limb
Inflow Bypass
Ipsilateral limb	2.8 %	2.8 %	0.970	<0.01
Contralateral limb	2.7 %	2.8 %	0.605	0.01
Outflow
PTA/Stent/Atherectomy	15 %	15 %	0.194	0.02
Ipsilateral limb	16 %	14 %	0.003	0.03
Contralateral limb
Outflow Bypass
Ipsilateral limb	7.3 %	6.3 %	0.001	0.04
Contralateral limb	7.1 %	5.9 %	<0.001	0.05
Major Amputation
Ipsilateral limb	0.6 %	0.4 %	0.048	0.02
Contralateral limb	4.0 %	3.0 %	<0.001	0.05
Minor Amputation
Ipsilateral limb	5.4 %	3.9 %	<0.001	0.07
Contralateral limb	4.1 %	2.7 %	<0.001	0.07

^*CAD=Coronary Artery Disease (yes= history of myocardial infarction but no symptoms, stable angina, unstable angina, or myocardial infarction in the past 6 months); CHF=Congestive Heart Failure; COPD=Chronic Obstructive Pulmonary Disease; ASA= American Society of Anesthesiologists; Other= asymptomatic indication in cases of bilateral common iliac treatment; Inflow= above common femoral (aorta, iliac, femoral); PTA= percutaneous transluminal angioplasty; Ipsilateral= treated side; Contralateral= opposite treated side; Outflow= below common femoral, infra-inguinal; Major= above or below knee (loss of foot); Minor= within foot.

^†Statistical significance for categorical/dichotomous variables determined using Chi-squared test and Student’s T-test for continuous characteristics.

^‡Absolute standardized difference = difference in means or proportions divided by standard deviation; imabalance in groups if its absolute value is greater than 0.1

Men and women differed slightly by indication for treatment (Table 1). Most interventions were performed for claudication, namely 59% and 53% of limbs treated in men and women, respectively (p<0.001). Rest pain was more prevalent in women, accounting for 16% of limbs treated amongst women compared to only 11% among men (p<0.001). Endovascular outflow procedures of the ipsilateral or contralateral limb were the most common previous interventions (15% of the cohort), but there were no meaningful differences in any prior procedure between men and women.

Number of Arteries Treated

The number of arteries treated per procedure ranged from one to six, with a median number of 1 artery treated per limb. By sex, 54% men versus 51% women had a single artery treated (p<0.001), 31% men versus 34% women had 2 arteries treated (p<0.001), and 15% men versus 15% women had 3 or more arteries treated (p=0.71).

When we assessed the relationship between the number of arteries treated and indication, we noted among unilateral limb treatment (Figure 2A) a minor sex difference in rest pain patients, where 43% of women had two or more arteries treated compared to 39% in men (p=0.04). However, men and women with claudication or tissue loss had a similar number of arteries treated. In bilaterally treated limbs (Figure 2B), there was a slight sex difference in number of arteries treated for claudication (one artery treated: 77% in men vs. 74% in women, p=0.01), but no significant difference in those treated for rest pain or tissue loss. Taken in aggregate across different indications for intervention, the number of arteries treated was not associated with sex.

Figure 2:

Number of arteries treated per limb by sex and indication in (A) unilaterally and (B) bilaterally treated limbs. This figure shows the effect of disease severity on the proportion of unilaterally and bilaterally treated limbs with multilevel disease in men and women.

Disease severity, however, was significantly associated with the number of arteries treated. Among all patients who had bilateral treatment, increasing severity from claudication to rest pain to tissue loss lead to a significant increase in multilevel disease treatment (2+ arteries treated; p for trend<0.001) and significant decrease in single artery treatment (p for trend<0.001).

Distribution of Arteries Treated

Men and women had a very similar distribution of arteries treated (Figure 3A). Figure 3B shows the proportion of treatments performed in men versus women at each artery level. Except for the aorta, the number of interventions at each artery level was higher in men than women. When calculating rates of treatment at artery levels, women were more likely to receive treatment in the aorta (RR=2.0, 95% CI: 1.6–2.5), common iliac artery (RR=1.2, 95% CI: 1.1–1.2), superficial femoral artery (RR=1.03, 95% CI: 1.00–1.06), and popliteal artery (RR=1.1, 95% CI: 1.0–1.1) Women were less likely to have treatment in the external iliac artery (RR=0.9, 95% CI: 0.8–0.9) and tibial arteries (RR=0.8, 95% CI: 0.76–0.82). Women and men were equally likely to receive treatment in the common femoral artery (RR=0.97, 95% CI: 0.9–1.1) and profunda femoris artery (RR=0.9, 95% CI: 0.7–1.0).

Figure 3:

(A) Overall and (B) within-artery distribution of arteries treated by sex. This figure shows the distribution of arteries treated in men and women, as well as the proportion of men versus women for each artery type treated.

We also studied sex differences in the distribution of common combinations of arteries treated at the limb level, while accounting for unilateral versus bilateral treatment (Data Supplement Table 1). We found no significant differences by sex.

Lesion Characteristics

Lesion characteristics included Transatlantic Inter-Society Consensus (TASC) score, treated length, occlusion length, and percent of lesions that were occluded (Table 2). Except in tibial arteries, TASC A lesions were the most commonly treated lesions, comprising between 30% of superficial femoral artery lesions treated to 56% of profunda femoris artery lesions treated. In the tibial arteries, TASC D lesions were the most common, accounting for 37% of all tibial artery lesions treated. Overall, men and women presented with similar TASC score lesions. Similarly, the mean occlusion length was similar in men and women (4.5 cm in men vs 4.6 cm in women, p=0.04). In general, at each artery level, men and women demonstrated similar lesion characteristics including TASC score, treatment length, occlusion length, and frequency of occlusion (Table 2).

Table 2.

Lesion characteristics of arteries treated.

Transatlantic Inter-Society Consensus (TASC) score
Artery Treated	A				B				C				D
	N	Men	Women	P-value	N	Men	Women	P-value	N	Men	Women	P-value	N	Men	Women	P-value
Common Iliac	78	45%	55%	0.475	69	35%	65%	0.184	24	21%	79%	0.031	74	42%	58%	0.942
External Iliac	4680	55%	45%	0.358	2001	54%	46%	0.952	998	52%	49%	0.043	858	54%	46%	0.960
Common Femoral	1974	63%	37%	0.125	1725	62%	38%	0.891	866	62%	38%	0.921	565	58%	42%	0.048
Profunda	652	60%	40%	0.254	335	61%	39%	0.411	261	57%	43%	0.567	124	50%	50%	0.040
SFA	204	61%	39%	0.637	80	63%	38%	0.893	37	62%	38%	0.967	28	64%	36%	0.783
Popliteal	3581	59%	41%	0.12	3446	59%	41%	0.054	2596	55%	45%	0.003	1939	56%	44%	0.205
Tibial	1701	56%	44%	0.997	1873	55%	45%	0.248	952	55%	45%	0.681	802	59%	41%	0.076

Artery Treated	Total Treated Length Mean (SD)			Total Occlusion Length Mean (SD)			% Lesions Occluded
	Men	Women	P-value	Men	Women	P-value	N Occluded	Men	Women	P-value
Common Iliac	6.1 (0.7)	5.4 (0.4)	0.365	3.2 (0.9)	2.3 (0.4)	0.308	132	40%	60%	0.557
External Iliac	4.5 (<0.1)	4.3 (<0.1)	<0.001	2.2 (<0.1)	2.0 (<0.1)	0.039	4,795	54%	46%	0.701
Common Femoral	5.4 (<0.1)	5.5 (0.1)	0.372	2.5 (0.1)	2.6 (0.1)	0.267	2,787	62%	38%	0.428
Profunda	0.8 (<0.1)	0.9 (<0.1)	0.250	0.5(<0.1)	0.6 (<0.1)	0.251	837	60%	41%	0.683
SFA	0.5 (<0.01)	0.6 (0.1)	0.066	0.2 (<0.1)	0.2 (<0.1)	0.705	173	59%	41%	0.289
Popliteal	13.2 (0.1)	13.4 (0.1)	0.216	8.2 (0.1)	8.3 (0.1)	0.466	7,948	57%	43%	0.938
Tibial	7.4 (0.1)	7.6 (0.1)	0.248	4.6 (0.1)	4.8 (0.1)	0.256	3,556	55%	45%	0.815

SFA= superficial femoral artery

Treatment Types Delivered

Treatment types studied included percutaneous transluminal angioplasty (PTA), self-expanding stent, balloon-expandable stent, stent graft, atherectomy (including laser atherectomy, orbital atherectomy, and excisional atherectomy), and other treatments (including cryoplasty and cutting balloon angioplasty). Across indication and artery treated, men and women received the same treatment modality, with few exceptions (Figure 4). For example, in superficial femoral arteries treated for claudication, 41% were treated with a self-expanding stent in men versus 36% in women (p=0.04). See Data Supplement Table 2 for detailed results.

Figure 4.

Treatment delivered by artery treated, sex, and indication (A) claudication, (B) rest pain and (C) tissue loss. This figure shows the distribution of treatment modalities delivered to each artery treated by artery type and indication for men and women.

Disease severity and artery treated appear strongly associated with treatment type delivered (Figure 4). Descending from the common iliac to the tibial arteries, there is a significant linear trend in the increase of PTA (p for trend<0.001) atherectomy (p for trend<0.001), and other treatment modalities (cutting balloon angioplasty or cryoplasty) (p for trend<0.001) across all indications. Likewise, descending from the common iliac to tibial arteries, there is a significant linear trend in the decreased use of self-expanding stent (p for trend<0.001), balloon-expandable stent (p for trend<0.001), and stent graft (p for trend<0.001) across all indications.

Discussion

The treatment of peripheral vascular disease in women has been suggested to present sex-specific challenges in technique and therefore initial approach.⁷ For example, some analyses found that women hospitalized for PAD are less likely to undergo a procedure, compared to men.¹¹ Further, female sex has been associated with worse outcomes following endovascular and open vascular procedures.^{12, 13} Yet differences in clinical and demographic factors have not been able to completely account for this noted sex bias in initial treatment presentation or treatment approach.⁶ We therefore sought to explore the underlying sex-based differences in the clinical presentation and endovascular treatment of patients with PAD using a large, validated quality improvement study cohort to address the lack of power and variation in information regarding patient, limb, and artery-specific data inherent to the current published literature.

We provide a brief overview of the most relevant sex-based studies in PAD patients in Table 3. As shown, there remains a fair amount of heterogeneity in the conclusions drawn while the limitations of each study make it difficult to draw any global conclusions in meta-analysis. This paucity of data leads to the current lack of consensus in the literature regarding sex-based differences among patients with PAD. Some of this conflict may be due to the pervasiveness of single-center, small sample studies with limited external validity on which prior literature conclusions are drawn.

Table 3.

Review of key literature in sex-based differences among patients with PAD

Author, Year	Summary of Findings (Men versus Women)	Limitations
Lo et al, 20141	Difference: Women older and have more advanced disease.	Limited clinical information Limited geographic sample
Pulli et al, 20127	Difference: Women older and less likely to be smokers. No difference: Hypertension, diabetes, coronary artery disease TASC C or D lesions Claudication or critical limb ischemia	Single-center European study Small sample (n=258)
Ortman et al, 201214	Difference: Women older, more hypertension, and less likely to smoke. Women more likely to have a femoropopliteal lesion, men were more likely to present with a tibial artery lesion. Women at higher risk for multilevel disease. No difference: occlusion length	Limited consideration of artery-level data Single-center European study Small sample (n=233)
Gallagher et al, 20114	Difference Women were older than men and had more rest pain More men were smokers, had CAD, and had claudication More women underwent intervention (PTA or PTA+ Stent) for critical limb ischemia No difference: Hypertension and diabetes Lesion length, TASC score, or lesion location (superficial femoral artery versus popliteal versus tibial)	Infrainguinal disease only Excluded key treatments (atherectomy) No comparison of treatment type

Our study was designed to systematically assess sex-based variation in PVI considering these shortcomings with the aim to support, supplant, or expand the current knowledge base. Our findings add to this current literature in several important ways (Table 4). First, regarding the initial clinical patient presentation, we found few meaningful sex-based differences in terms of comorbidities or history of previous interventions. As such, our study reaffirms previously reported literature results. It appears consistent across ours and other authors’ work that women more commonly present at an older age with more advanced disease, such as ischemic rest pain versus claudication, when compared to men. We also noted that men more commonly smoke or previously smoked compared to women. On the other hand, while current literature was inconclusive on sex differences in comorbidities such as hypertension, our much larger cohort showed no such differences. It is unclear whether socioeconomic or genetic factors are attributable in this consistent discrepancy in initial presentation.

Table 4.

Comparison of study findings and literature in context of study objectives

Study Objective	Summary of Literature (Men versus Women)	Our Findings
Patient Presentation
Age	Women present at an older age1, 4, 11–14	Confirms women present at an older age.
Hypertension	No difference in hypertension4, 14 Women present with more hyptertension14	Confirms no difference in hypertension.
Smoking	Men smoke more4, 7, 14	Confirms men smoke more.
Disease Characteristics
Indication	Women had less claudication and more critical limb ischemia1, 4, 11, while other reports suggest no difference in claudication and critical limb ischemia7	Confirms women had less claudication and more rest pain.
TASC Score	No difference in TASC score4, 7	Confirms no difference in TASC score.
Multilevel disease	Women had multilevel disease14	Found no difference in number of arteries treated.
Occlusion Length	No difference in occlusion length14	Confirms no difference in occlusion length.
Treated Length	No difference in treated length4	Confirms no difference in treated length.
Artery Treated	Women: iliac lesions and iliac/femoropopliteal plus tibial artery treatments Men: isolated tibial artery treatments14	Found negligible difference in artery location treated.
Treatment Modality
Angioplasty	No studies identified	Found negligible sex differences in treatment modality delivered. Disease severity and lesion location predictive of treatment modality.
Stenting
Atherectomy

Second, in terms of disease characterization, few single-center studies^{4, 14} briefly addressed sex differences in lesion characteristics. As listed in Table 4, they suggest that men more commonly have tibial disease while women more commonly have iliac disease, although others report no difference in TASC score or lesion length. Yet these analyses did not account for disease severity or disease location, i.e. the type of artery that was treated, which may ultimately bias results. Our study was able to account for these confounders and noted no sex differences in disease characteristics regarding lesion length, occlusion length, or disease distribution as measured by TASC score or the type of artery treated.

Third, sex differences in endovascular treatment modality used in PVI have not been previously addressed in the literature (Table 4). Our meticulous analysis comparing various treatment types by sex found that there were no significant differences in men compared to women. However, we found a clear and persistent trend in the increasing use of PTA with a concomitant decline in the use of stents and/or atherectomy as the treated arteries became more distal. This finding objectively confirms a common notion that smaller caliber vessels are less likely to receive stent placement or atherectomy and are more likely treated with PTA only. Thus, rather than sex, the disease location and distribution was the major determinant of treatment type. Future work will examine how these decisions contribute towards treatment outcomes in PVI.

In addition, we identified a significant association between indication for treatment, or disease severity as assessed by rest pain versus tissue loss versus claudication, and the number of arteries treated. Similarly, disease severity was also strongly linked to the treatment modality employed. In essence, the worse the disease process, the more aggressive the treatment as described by number of arteries treated and treatment modality employed. The interaction of these characteristics has not been previously reported, but seems often intuitive in the decision-making process regarding limb ischemia treatment.

Limitations

This paper serves as a real-world description of practice patterns among 24,000 men and women undergoing PVI across the United States. Although this cohort lacked significant representation from all racial and ethnic groups since most patients were Caucasian (83%) and non-Hispanic (96%), this might be the true representation of patients receiving PVI treatment and is in and of itself an important finding in health disparities studies. Furthermore, women represented a substantial (42%) proportion of the cohort, which is an uncommon strength in vascular disease studies.

Reported frequencies were not adjusted for patient risk factors given the descriptive nature of this project. To address potential confounding, we stratified by indication and artery type treated where appropriate. Additionally, since this is an observational cohort study, causality cannot be assumed in proposed associations.

Missing data is a limitation inherent to large registries. Any procedures that were missing critical information such as sex, indication, and artery type treated were excluded from the outset, but comprised a small proportion of the cohort. No variables analyzed were missing more than 5% of observations except TASC score, which was missing in about 10% of artery-level observations. To address this limitation, a stratified analysis of procedures by missing versus completed TASC classification was conducted for sex, indication, and artery type treated for which there was no statistically significant differences.

Conclusions

In summary, we identified that women clinically present at an older age with more advanced arterial disease, but are less likely to have comorbid coronary artery disease or be actively smoking. These differences could be due to a varied disease pathophysiology or represent limitations to healthcare access, among others, for women compared to men and thus warrant further study. For instance, our future endeavors will analyze the associations between sex disparities in PAD treatment and post-procedural outcomes with emphasis placed on regional variations and socio-economic status as predictive variables.

Men and women who undergo endovascular treatment for PAD in our national registry are largely equivalent in terms of disease characterization and treatment modality. Sex-based disease characterization in terms of number of arteries treated and artery type treated appears to be driven by indication. Likewise, treatment modality seems associated with indication and artery type treated, rather than sex. Further investigation is required to appreciate the effect of disease severity and treatment modality on patient outcomes after PVI.

What is Known

• Studies suggest that women diagnosed with peripheral arterial disease are treated at an older age, present with advanced multilevel disease, and have poorer overall health.

• Yet these investigations have limited descriptions of clinical indications, treatment modalities, and disease distribution by sex in addition to being underpowered to detect sex differences.

What The Study Adds

Using a large, national vascular registry of which 42% are women, this study:

• Confirms that women present at an older age with more advanced disease;

• Finds no sex differences in disease characteristics including lesion length, occlusion length, TASC score and the type of artery treated;

• Identifies no sex differences in treatment type-instead, treatment modality driven by TASC score and artery treated.